The present invention relates to novel N-substituted .alpha.-amino acids and derivatives thereof useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds, and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. More particularly, the novel compounds of the present invention selectively block the N-methyl-D-aspartate (NMDA) excitatory amino acid receptors in mammals. Thus, the compounds of the present invention are useful for treating diseases responsive to blockade of excitatory amino acid receptors. For example, the compounds of the present invention are useful in the treatment of cerebrovascular disorders such as cerebral ischemia, or cerebral infarction resulting from a range of conditions such as thromboembolic or hemorrhagic stroke, cerebral vasospasm, hypoglycemia, cardiac arrest, status epilepticus, and cerebral trauma. Additionally, the compounds of the present invention are useful in the treatment of schizophrenia, epilepsy, neurodegenerative disorders, Alzheimer's disease or Huntington's disease. Further, the compounds of the present invention are useful as anesthetics, particularly in surgical procedures where a finite risk of cerebrovascular damage exists.
A series of unsaturated amino acids which are antagonists of excitatory amino acid receptors sensitive to NMDA is disclosed in European Patent Application Number 0233154.
A series of substituted .alpha.-amino acids which are useful for treating epilepsy, disorders associated with excess GH or LH secretion, schizophrenia, depression, CNS degenerative disorders and cerebral hypoxic conditions is disclosed in Great Britain Patent Number 2156818A.
A series of hetero alkyl phosphonic acid derivatives of 2-piperidine or 2-tetrahydropyridinecarboxylates and esters thereof which are useful for the treatment of disorders responsive to blockade of the NMDA receptors in mammals is disclosed in U.S. Pat. No. 4,746,653.
A series of novel substituted .alpha.-amino acids which have utility for treating disorders which benefit from blockade of aspartate and glutamate receptors is disclosed in copending U.S. Ser. No. 256,221, filed Oct. 14, 1988 which is a continuation-in-part of U.S. Ser. No. 126372, filed Nov. 30, 1987.
However, the compounds disclosed in European Patent Application Number 0233154, Great Britain Patent Number 2156818A, U.S. Pat. No. 4,746,653, and copending U.S. Ser. No. 126372 do not suggest or disclose the combination of structural variations of the compounds of the present invention described hereinafter.